The Planetary Boundaries (PB) framework represents a significant advance in specifying the ecological constraints on human development. However, to enable decision-makers in business and public policy to respect these constraints in strategic planning, the PB framework needs to be developed to generate practical tools. With this objective in mind, we analyse the recent literature and highlight three major scientific and technical challenges in operationalizing the PB approach in decision-making: first, identification of thresholds or boundaries with associated metrics for different geographical scales; second, the need to frame approaches to allocate fair shares in the ‘safe operating space’ bounded by the PBs across the value chain and; third, the need for international bodies to co-ordinate the implementation of the measures needed to respect the Planetary Boundaries. For the first two of these challenges, we consider how they might be addressed for four PBs: climate change, freshwater use, biosphere integrity and chemical pollution and other novel entities. Four key opportunities are identified: (1) development of a common system of metrics that can be applied consistently at and across different scales; (2) setting ‘distance from boundary’ measures that can be applied at different scales; (3) development of global, preferably open-source, databases and models; and (4) advancing understanding of the interactions between the different PBs. Addressing the scientific and technical challenges in operationalizing the planetary boundaries needs be complemented with progress in addressing the equity and ethical issues in allocating the safe operating space between companies and sectors.